The aim of this research is to study in detail how a group of four regulatory proteins of Saccharomyces cerevisiae control the expression of genes in a position dependent manner. Specifically there are silent copies of the mating type locus genes of Saccharomyces cerevisiae that are not expressed due to the products of the four SIR genes. These silent copies serve as a source of genetic information that is transposed to the mating type locus when cells switch from one mating type to another. In addition, the mechanism by which these proteins enter the nucleus after being synthesized in the cytoplasm will be studied. The position effect experiments will entail a genetic analysis of mutants that fail to repress the silent mating type loci. Extragenic suppressors of these mutations will be studied in order to learn how the four proteins interact to control these loci and what the mechanism of this regulation is. Entry of proteins into the nucleus will be studied by selecting mutants that block entry of a foreign endonuclease into the nucleus. The medical significance of this work is two fold. With the opportunity for gene therapy rapidly approaching, it will be important to understand how the location of a gene can influence the expression of that gene. The entry of proteins into the nucleus is significant because all proteins involved in replicating DNA and transcribing genes must enter the nucleus. Furthermore, the oncogene products from some tumor viruses exert their influence after entering the nucleus. It will be important to identify the routes of nuclear entry before we can evaluate the possibility of regulating it.